Pedro Amariles

Revisión de tests de medición del cumplimiento terapéutico utilizados en la práctica clínica

El incumplimiento farmacoterapéutico constituye un importante problema asistencial que puede afectar a la salud de los pacientes, y es una de las posibles causas del fracaso de los tratamientos. Cada fármaco que se comercializa ha necesitado un gran esfuerzo e inversión, que puede resultar en vano si el enfermo no lo utiliza como debe1,2. La falta de cumplimiento de la pauta terapéutica es un fenómeno común, sobre todo en procesos crónicos, y en ocasiones las razones que conducen a esta conducta son complejas y se basan en el complicado proceso del comportamiento humano3. Actualmente, el incumplimiento del tratamiento farmacológico es la causa del fracaso de muchos tratamientos y conlleva serios problemas en calidad de vida, costes para el sistema de salud y, sobre todo, contribuye a que no se consigan resultados clínicos positivos4. La Organización Mundial de la Salud (OMS) considera la falta de cumplimiento de los tratamientos crónicos y sus consecuencias negativas clínicas y económicas un tema prioritario de la salud pública5. Para facilitar la valoración del cumplimiento, se dispone de una serie de métodos apoyados en la entrevista clínica, en los que, de forma directa, se le pregunta al enfermo sobre su cumplimiento. Estos procedimientos son métodos muy fiables si el paciente se confiesa mal cumplidor y, por tanto, poseen un alto valor predictivo positivo. No obstante, al comparar este método con otros más exactos, se observa que hay un número importante de enfermos que mienten cuando dicen que toman toda la medicación (bajo valor predictivo negativo)6. Es evidente que la identificación de los pacientes incumplidores resulta fundamental; por ello, los profesionales de la salud deben aplicar estos métodos, incorporándolos a la práctica asistencial diaria7. Se plantea una revisión para identificar qué tests se utilizan en la valoración del incumplimiento terapéutico, que sean aplicables, sencillos y que no requieran de un gran esfuerzo y tiempo en la práctica clínica por los profesionales de la salud.También se plantea sugerir qué método o combinación de métodos serían más prácticos, ágiles e idóneos para valorar el cumplimiento terapéutico en atención primaria. Se ha realizado una revisión bibliográfica durante el mes de mayo de 2007 en las bases de datos Medline (PubMed), y en las referencias de los artículos considerados relevantes, para obtener estudios publicados sobre incumplimiento de la medicación. En la estrategia de búsqueda se utilizaron los términos «compliance and drug» y «adherence and drug», en títulos o resúmenes, publicados entre enero de 1990 y mayo de 2007, en artículos en los que la medición del cumplimiento se realizó mediante entrevista clínica (test de incumplimiento). Además, se llevó a cabo una búsqueda en distintas fuentes primarias y en tesis doctorales publicadas en ese mismo período. Los tests encontrados que presentan posibilidades para su aplicación en la práctica clínica se describen a continuación.

Interacciones medicamentosas: aproximación para establecer y evaluar su relevancia clínica

La identificacion, prevencion y tratamiento de las interacciones medicamentosas clinicamente relevantes son aspectos fundamentales en la farmacoterapia. En este trabajo se ha pretendido sistematizar la informacion y desarrollar una propuesta para establecer y evaluar la relevancia clinica de las interacciones medicamentosas. Se realizo una revision bibliografica en Medline y PubMed, y en las referencias de los articulos considerados relevantes. En los titulos y resumenes de los articulos se busco el termino «interacciones medicamentosas» combinado con «relevante clinicamente», «relevancia clinica» o «relevante significativamente». Se incluyeron las publicaciones realizadas en humanos, en ingles o espanol, entre enero de 1996 y junio de 2006. Se presentan el tipo y mecanismo de las interacciones medicamentosas, especialmente las asociadas a cambios en el aclaramiento sistemico y en la biodisponibilidad; se propone una secuencia de pasos a seguir para establecer la relevancia clinica de las interacciones y una clasificacion basada en la gravedad y probabilidad de aparicion.

Magnitude of the white-coat effect in the community pharmacy setting: The MEPAFAR study

BACKGROUND There is little information regarding the community pharmacy blood pressure (CPBP) measurement method and their differences with home (HBP) or ambulatory BP (ABP). The aim of this study was to measure such differences and their variation over successive visits. METHOD Cross-sectional study carried out in eight pharmacies in Gran Canaria (Spain). The study included 169 treated hypertensive patients. BP was measured at the pharmacy (four visits), at HBP (4 days) and 24-h ABP monitoring. We defined pharmacy white-coat effect (PWCE) as differences between CPBP and HBP (home PWCE) or daytime ABP (ambulatory PWCE). RESULTS The overall (pooled values for all visits) ambulatory PWCE was not significantly different from zero for systolic BP (SBP) (-0.4 mm Hg (95% confidence interval (CI): -1.8 to 1.1)), but greater than zero for diastolic BP (DBP) (3.4 mm Hg (95% CI: 2.3 to 4.6)). The overall home PWCE was not significantly different from zero, both for SBP (1.2 mm Hg (95% CI: -0.1 to 2.6)) and DBP (0.1 mm Hg (95% CI: -0.7 to 1.0)). The ambulatory and home PWCE on the first visit were greater than zero (P < 0.001) (SBP/DBP): 3.5/4.8 and 1.9/1.5 mm Hg, respectively; but showed important reductions at the second visit and became not significantly different from zero, except the ambulatory PWCE in DBP, which persisted until the last visit. CONCLUSION The trend in the PWCE decreased over the successive visits to the pharmacy. Only the ambulatory PWCE in DBP proved to be statistically greater than zero after the second visit. Repeated CPBP measurements could be a useful alternative to assess the response to antihypertensive treatment.

Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

BackgroundHighly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection.Methods/designRandomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals.DiscussionPreliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these findings warrant further evaluation to determine if long-term administration of statins may benefit the virological and immunological evolution in HIV-1-infected individuals before the use of antiretroviral therapy is required.Trial registrationRegistration number NCT00721305.

Efecto de la actuación farmacéutica en la adherencia del tratamiento farmacológico de pacientes ambulatorios con riesgo cardiovascular (Estudio EMDADER-CV-INCUMPLIMIENTO)

OBJECTIVE To evaluate the effect of pharmacist involvement, by means of Pharmacotherapy Follow-Up (PFU) in the improvement of medication adherence and therapeutic outcomes. DESIGN An experimental, controlled, and randomised clinical study comparing a PFU program with the routine process in Spanish community pharmacies improved with health education during 8 months. SETTING Nine Spanish community pharmacies. PARTICIPANTS Patients between 25 and 74 years with a moderate-high cardiovascular risk (CVR), who arrived with a prescription, in their name, for drugs for at least one CVR factor. INTERVENTIONS The patients were randomly assigned to the intervention group (IG), and received PFU and health education, or the control group (CG), who received health education only. MAIN MEASUREMENTS Adherence to treatment, and blood pressure (BP) and total cholesterol (TC) levels at the beginning and end of the study. RESULTS Of the 87 patients enrolled, 85 finished the study: 41 from the CG and 44 from the IG. Both groups increased adherence at the end of the [CG: 26.9%; 95% CI: 12.7- 41; IG: 27.3%; 95% CI: 13.6 - 41]. Although the IG showed better results in the variation of BP and TC levels, the differences compared to the CG were not statistically significant. CONCLUSIONS PFU and health education improves adherence to treatment. To be a patient who completes the study is also associated with improvement in the blood pressure and blood pressure/total cholesterol objectives.

Clinical value of blood pressure measurement in the community pharmacy

Aim of the study To investigate whether the measurement of blood pressure in the community pharmacy is a valuable method to diagnose hypertension, to assess the need and the effectiveness of anti-hypertensive treatments, or, in general, to make clinical decisions. Method Information has been extracted from articles published in English and in Spanish, from January 1989 to December 2009, in indexed magazines in MEDLINE and EMBASE. To perform the search, multiple and specified terms related to the community pharmacy setting, to blood pressure measurement and to the comparison and agreement between blood pressure measurement methods were used. Selected articles were those that: (1) compared and/or measured the agreement (concordance) between community pharmacy blood pressure measurements obtained in repeated occasions, or (2) compared and/or measured the agreement between the community pharmacy blood pressure measurement method and other measurement methods used in clinical practice for decision-making purposes: blood pressure measurement by a physician, by a nurse and home or ambulatory blood pressure monitoring. Articles were included and analyzed by two investigators independently, who essentially extracted the main results of the manuscripts, emphasizing the assessment of the blood pressure measurement methods used and the completed statistical analysis. Results Only three studies comparing the community pharmacy blood pressure measurement method with other methods and one comparing repeated measurements of community pharmacy blood pressure were found. Moreover, these works present significant biases and limitations, both in terms of method and statistical analysis, which make difficult to draw consistent conclusions. Conclusion Further research of high quality is needed, which results can guide the clinical decision-making based on the community pharmacy blood pressure measurement method.

Interacciones medicamentosas en pacientes infectados con el VIH: aproximación para establecer y evaluar su relevancia clínica

Objetivo: Sistematizar informacion sobre interacciones medicamentosas en pacientes con VIH/sida, y verificar la funcionalidad de una propuesta para definir y evaluar la relevancia clinica de las interacciones, especialmente las farmacocineticas. Metodo: Se realizo una revision en PubMed de articulos publicados en ingles o espanol, entre enero de 1995 y junio de 2007, sobre interacciones de antirretrovirales en humanos. La estrategia de busqueda fue: drug interactions and anti-retroviral agents (or drugs), en el titulo y resumen. La busqueda fue complementada con la revision de interacciones de medicamentos utilizados frecuentemente en pacientes con VIH/sida y de referencias de articulos considerados relevantes. Finalmente, se siguio una propuesta para definir y evaluar la relevancia clinica, basada en la probabilidad de ocurrencia y en la gravedad de la interaccion. Resultados: Se identificaron 378 articulos, de los que se pudo acceder al texto completo de 296. Para pacientes con VIH/sida, se desarrollo el tipo y mecanismo de las interacciones; se evaluo y definio la relevancia clinica de las interacciones, con base a una propuesta definida previamente. Entre las interacciones farmacocineticas de relevancia clinica, cerca de un 80% estuvieron relacionadas con cambios en el aclaramiento sistemico [debidos a la inhibicion o a la induccion sistemica de la actividad metabolica del citocromo P-450 3A4 (CYP3A4)]; mientras que un 15% con cambios en la biodisponibilidad [variaciones en el pH gastrointestinal, en el aclamiento presitemico (mediado por la CYP3A4) o en la actividad de la glicoproteina-P (Gp-P)]. Conclusiones: En los pacientes infectados con el VIH/sida, la mayoria de las interacciones farmacocineticas de relevancia cinica se deben a la inhibicion o induccion de la actividad metabolica sistemica del higado.

Risk factors associated with NSAID-induced upper gastrointestinal bleeding resulting in hospital admissions: A cross-sectional, retrospective, case series analysis in valencia, spain

UNLABELLED Abstract. BACKGROUND NSAIDs are a significant cause of drug-related hospital admissions and deaths. The therapeutic effects of NSAIDs have been associated with the risk for developing adverse events, mainly in the gastrointestinal tract. OBJECTIVES The focus of this study was to identify the most common risk factors associated with NSAID-induced upper gastrointestinal bleeding (UGIB) resulting in hospital admissions. A secondary end point was the relationship between use of gastroprotective treatment and relevant risk factors to NSAID-induced UGIB in the selected population. METHODS This study was a cross-sectional, retrospective, case-series analysis of NSAID-induced UGIB resulting in hospital admission to the Requena General Hospital, Valencia, Spain, occurring from 1997 to 2005. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify UGIB admissions associated with NSAIDs. To estimate the probability of association between UGIB and the use of NSAIDs, the Naranjo adverse drug reaction probability was used. Patients were categorized as high-risk to develop UGIB if they met ≥1 of the following risk criteria (relevant risk factors): aged ≥65 years (age risk factor); peptic ulcer disease or NSAID gastropathy occurring in the year before their hospital admission (history risk factor); and concomitant use of other NSAIDs, systemic corticoids, oral anticoagulants, or platelet aggregation inhibitors (concomitant medication risk factor). Patients were categorized as candidates to use gastroprotections if they met ≥1 of the relevant risk factors. Patients were categorized as users of gastroprotective treatment if they used proton pump inhibitors, histamine H2-receptor antagonists, or misoprostol at hospital admission. RESULTS This study comprised 209 cases of NSAID-induced UGIB (129 men, 80 women: mean [SD] age, 71.5 [13.8] years; 128 [61.2%] receiving acetyl salicylic acid [ASA], with 72 [34.4%] receiving low-dose [80-325 mg] ASA). Prevalence of relevant risk factors for UGIB were as follows: age, 158 (75.6%) patients; history, 37 (17.7%); and concomitant medication, 35 (16.7%). One hundred seventy-eight (85.2%) patients met ≥1 criterion for using a gastroprotective agent; 28 (15.6%) were actually using one. Only the history risk factor was significantly associated with the use of gastroprotective treatment (P = 0.007; odds ratio = 3.17). CONCLUSIONS In this study of NSAID-induced UGIB resulting in hospital admission, age was the most common risk factor. However, this criterion was not associated with the use of gastroprotective agents. A large number of cases were associated with the use of ASA, primarily in those receiving low doses. A significant lack of gastroprotective agent use was observed in patients who met the criteria to use them.

Interacciones medicamentosas de agentes hipolipemiantes: aproximación para establecer y valorar su relevancia clínica: revisión estructurada

Objective: To carry out a structures review of drug interactions of hypolipidemic drugs and to assess their clinical relevance. Method: Structured review of drug interactions of hypolipidemic drugs in humans through PubMed/Medline of published articles, without language restrictions and with full text access until June 30th of 2012. The following Mesh terms were used: Drug Interactions, Lipid Regulating Agents, Herb-Drug Interactions, Food-Drug Interactions y Hypolipidemic Agents (Pharmacological Action). The information was completed with those articles considered to be relevant. Finally, a method was used to assess the clinical relevance of the interaction, based on the likelihood of occurrence and the severity of the effect of the interaction. Results: 849 publications were gathered, of which 243 references were selected, among which 189 interactions were identified. Thirty-three of them were considered of very high risk (level 1) and 42 of high risk (level 2), basically associated to increased risk for rhabdomyolisis. Enzymatic inhibition of CYP450 was the most common mechanism for these interactions. Conclusions: Of the interactions identified in patients on hypolipidemic drugs, 60.3% (128/189) are clinically relevant (very high or high risk), mainly associated to the occurrence of rhabdomyolisis. Most of these interactions are attributed to simultaneous use of CYP3A4 inhibitors. Therefore, statins metabolized through CYP3A4 (simvastatin, lovastatin and atorvastatin) are the ones with the highest number of clinically relevant interactions.

Application of the SCORE and Wilson–Grundy methods for the assessment of cardiovascular risk in community pharmacies

Background:  The assessment and follow‐up of patients with risk factors, or with cardiovascular disease (CVD), involves estimating and monitoring their CVD risk (CVDR). There are different opinions about the most appropriate method for this.